Various studies have demonstrated the unique regenerative properties of the olfactory nerve. In intact nerves, the neurons turn over constantly and following injury to axon the entire nerve cell degenerates and is replaced by a new neuron differentiating from the mucosal basal cells. The mechanisms responsible for these properties will be studied in the garfish olfactory system. The 30 cm long garfish olfactory nerve is constituted of 12 million unmyelinated unbranched C fibers and is particularly well-suited for axonal transport and regeneration studies. A technique has been developed to isolate the olfactory perikarya from the mucosal tissue. It is therefore possible to follow the reactions to a nerve injury simultaneously in the cell body and in the axon. Previous studies have shown that following nerve crush near the mucosa, three populations of regenerating fibers appear in the nerve successively. The objectives of the proposed research are: 1) The continued characterization of degeneration and regeneration on the garfish olfactory nerve: a) the rate and composition of the various phases of axonal transport will be determined in regenerating nerve using techniques developed previously to study axonal transport in intact nerves. Since there is biochemical and electrophysiological evidence that most rapidly regenerating fibers are structurally and functionally immature, we will determine if the various phases of axonal transport are able to increase their rate sufficiently and/or alter their composition to meet all the demands of rapid growth; b) in a parallel study, the responses of the cell body will be analyzed: the time-course, quality and quantity of protein synthesis during cell death and during cell regeneration will be studied. 2) The investigation of the factors regulating cell death and cell neogenesis; a) the onset of cell death as a function of distance from the cell body to the site of injury will be studied; b) the origin and nature of the signal-inducing basal cell mitosis and differentiation will be examined as well as the hypothesis put forward to explain the various phases of regeneration.